Regenerative Medicine: A New Path for ALS Treatment
A first-of-its-kind stem cell therapy for ALS passes a critical safety benchmark, advancing the search to slow down, reverse and prevent the disease. In a parallel study, investigators are growing patient-derived stem cells to model ALS, hoping to uncover its mechanisms and classify it with more specificity. Can the cure to this degenerative condition lie in the endlessly regenerative power of stem cells?
First, her hands stiffened. Then she developed a limp. Ashley Fisher was 48 when she was diagnosed with amyotrophic lateral sclerosis (ALS). During the following three years, as the unstoppable disease took hold of her body, she lost the ability to work, hike by the beach or shop swap meets on Saturday mornings. So, she sought out what she could do with the time she had left: She enrolled in a clinical trial.
Even after paralysis stole her speech, Ashley consented to a five-hour spine operation, took immunosuppressive drugs for a year and underwent extensive testing at Cedars-Sinai’s ALS Clinic, where a team monitored the impact of the procedure on her body—specifically, one of her legs. Their goal: to test the safety of a combination stem cell/gene therapy to treat the rare neurodegenerative disease, caused by the unexplained, unstoppable death of motor neurons in the brain and spinal cord.
Moments after Ashley’s death, in May 2021 at a hospital in Oregon, her daughter, Courtney Fisher Olsen, relayed to a nurse the urgent instructions impressed upon her in the previous months: Call Cedars-Sinai and ask them to collect Ashley’s spinal tissue.
“She made this research a priority, and she was really proud of it,” Courtney says. “She would do anything to be part of finding answers.”
Ashley, along with the 17 others in the study, gave investigators their only opportunity to make a critical advance: The trial proved, for the first time, the safety of the implantation into the lumbar spinal cord of specialized stem cells—neural progenitors—engineered to express a powerful growth factor known to protect neurons. The findings, published in September 2022 in Nature Medicine, cleared investigators to study the therapy’s efficacy and continue refining the approach they hope that, ultimately, will slow or stop the disease.
These patients are the heroes of this research. They knew we weren’t going to cure their disease, only pursue whether the cells and this surgical approach were safe. We are encouraged enough by this approach to proceed in an attempt to slow disease progression.”
“These patients are the heroes of this research,” says Richard Lewis, MD, director of the Electromyography Lab and principal investigator of the study at the ALS Clinic. “They knew we weren’t going to cure their disease, only pursue whether the cells and this surgical approach were safe. We are encouraged enough with the results to proceed to more patients and attempt to slow disease progression.”
Until now, ALS has frustrated researchers with a notoriously impenetrable monolith. Only 5% to 10% of patients carry genes known to cause the disease. Without the ability to biopsy brain and spinal tissue, little is understood about its mechanisms. In the absence of biomarkers, physicians can only diagnose ALS after it has already taken hold, and the three Food and Drug Administration approved treatments do little to slow its progression. The highly specialized, resourceful clinicians at Cedars-Sinai’s ALS Clinic, an ALS Association Certified Treatment Center of Excellence, can only leverage tools and technologies to support their chief goal: to preserve quality of life as patients become paralyzed and die.
Buoyed by breakthroughs in the study of stem cells, Cedars-Sinai investigators are challenging assumptions and evolving their questions about ALS.
Because fresh progress in the disease is fueled by the body’s cells at their most naive state, the ALS Clinic team has embarked on a new clinical trial to test the safety of stem cell implantation directly into the cerebral cortices of ALS patients. Scientists are growing cells from ALS patients in petri dishes to model the disease.
Having built the largest library of hyper-specific disease data, the team is reconsidering whether ALS is not one disease but a collection of conditions.
They aim to differentiate between genetic and sporadic forms of ALS, and scour the models for the earliest signs of cellular decline.
Every approach takes square aim at the ultimate questions: Why do patients develop ALS, and how can we stop the suffering?
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